| In long-term space flight,the cognitive function decline caused by factors such as weightlessness and alternant biorhythms in space has seriously affected the astronaut's operational ability and the completion of space flight missions.Carrying out research on cognitive impairment mechanisms under this condition,looking for protective measures,improving the body's adaptability under special aerospace environments,and protecting astronauts' physical and mental health to the greatest extent are the primary task in the field of space medicine.Cognitive functional decline induced by environmental stress in space is reversible before cognitive impairment,and timely intervention can prevent it from turning into disease.However,the functional decline mechanism caused by stress is complex,and the target is not clear,making it difficult for modern medicine to take effect.Traditional Chinese medicine emphasizes the overall approach,syndrome differentiation,and treatment.It plays a role in health maintenance by regulating the body's resistance to exogenous noxious stimuli and has unique advantages in protecting functional cognitive decline caused by stress.Long-term clinical practice has shown that traditional Chinese medicines such as ginseng have delayed aging,anti-fatigue,and promoting learning and memory.Pharmacological studies have shown that ginsenoside Rgl and ginseng Rbl are the main active ingredients and can improve cognitive impairment caused by various stresses.Therefore,this paper will adopt two recognized aerospace stress models(simulated weightlessness model,chronic sleep deprivation model)and seven different types of behavioral evaluation methods(object recognition,Y maze,Step through,Step down,shuttle box,Morris water maze,Reward conditioned reflex)to evaluate the learning and memory ability of the model,study the improvement and action characteristics of different types of ginsenosides after the intervention,and then to explore its possible mechanism.1.Study of weightlessness effect simulation induced cognitive behavior and its characteristics.(1)Based on the principle of spontaneous activity(object recognition,Y maze):the percentage of spontaneous alternation of animals undergoing simulated weightlessness for two weeks and four weeks did not change significantly,and the working memory ability of animals was not affected after the simulated weightlessness was induced for two to four weeks.In the object recognition experiment,the discrimination index of the two-week model animal was significantly reduced,suggesting that the new object recognition ability was impaired considerably in two weeks.(2)Based on the principle of punishment(Step-through,Step-down,shuttle box,Morris water maze):in the Step-down experiment,the acquisition stage:the two-week and four-week model animals were significantly extended the latency,and the safety zone time was shortened considerably,showing the ability to learn to avoid electric shocks Poor.In the consolidation phase,the latency for the two-week and four-week model animals to jump off the stage was significantly shortened,and the safe zone time was significantly shortened,showing poor memory of the safe zone.In the Step through experiment,the latency of the two-week and four-week model animals at this stage was greater than 180s,which may be due to the insufficient driving force of the animals to darken,so the Step through experiment is not suitable for this model evaluation.In the shuttle box experiment,after two weeks of simulated weightlessness,the number of avoidances of the animals decreased,the number of escape failures increased significantly,and the safety zone time was significantly shortened,suggesting that the model animals have decreased associative learning and memory capabilities.In the water maze experiment,the latency of the two-week and four-week simulated weightlessness model animals was significantly increased,and the target quadrant distance ratio and target quadrant time ratio were significantly decreased,indicating that the spatial memory ability was impaired.(3)Based on the principle of Reward:set the lever operation-multiple color signal recognition-rewards for the first time to obtain the reward operation task of the integrated linkage,and detect the learning and memory behaviors such as decision-making and signal recognition when the simulated weightless animal performs the operation task,which is suitable Astronauts complete complex operations during space flight.This study showed that after four weeks of simulated weightlessness,the number of nose pokes and lever presses of simulated weightless rats in the single-operation conditioned reflex mode was significantly reduced,the completion time and the operation latency were prolonged,and the discrimination index in the signal recognition mode was significantly reduced,and the simulated weightlessness effect.It had a certain impact on animals' complex operation ability,attention,decision-making ability,signal recognition ability,etc.The reward manipulation conditioned reflex experiment could be used to accurately evaluate the cognitive changes caused by simulated weightlessness in complex manipulation conditioned reflex tasks,and it may be widely used in the study of cognitive function changes in future space flights.2.Improvement of protopanaxatriol-type ginsenosides(Rg1,PPT)and protopanaxadiol-type ginsenosides(Rbl,PPD)on spatial and associative learning and memory abilities of the simulated weightlessness effect model.Results showed that ginsenosides Rg1/Rbl(30,60 ?mol/kg)and their aglycones had a certain improvement effect on simulate weightlessness-induced cognitive decline.The changes of neurotransmitter and protein expression levels in the hippocampus were measured by liquid mass spectrometry and western blot.It was found that the improvement effect of ginsenosides Rgl and Rbl on learning and memory impairment caused by simulated weightlessness related to the regulation of the level of neurotransmitters such as Ach,DA,5-HT,and Glu,the balance of mitochondrial division and fusion,the inhibition of the process of cell apoptosis,and the enhancement of synaptic plasticity.3.Improvement of ginsenosides Rgl and Rbl on complex operation ability changes.After training the animal for a single operation conditioned reflex,the qualified animals were screened,and then simulated weightlessness induction was carried out for four weeks.The reward operation conditioned reflex experiment was carried out(including single operation conditioned reflex,reverse operation,and visual signal recognition three modes).Experimental results showed that administration of ginsenosides Rg1(30,60?mol/kg)and Rb1(30,60 ?mol/kg),and huperzine A(0.1 mg/kg)for two weeks could improve the exploration interest,attention,operation execution of animals to a certain extent.Among them,the improvement effect of ginsenoside Rg1 was more significant.Further examination of tissues in the prefrontal cortex,an important brain area for animal executive functions,by HE staining,liquid-mass spectrometry,and western blotting experiments.It showed improvement of ginsenosides Rgl and Rbl on complex operation tasks related to the regulation of oxidative stress,mitochondrial oxidative phosphorylation,cell apoptosis,and synaptic plasticity by the BDNF-TrkB/PI3K-AKT pathway.At the same time,Rg1 has a better regulatory effect than Rb1 by the BDNF-TrkB/PI3K-AKT signaling pathway,which may be one of the reasons why Rg1 plays a better role in improving the ability to operate tasks.4.Improvement effect of ginsenosides Rgl and Rbl on cognitive decline caused by sleep deprivation.Two weeks of roller sleep deprivation-induced changes in animal cognitive function and two weeks of intragastric administration of ginsenosides Rg1(30,60 ?mol/kg)and Rb1(30,60 ?mol/kg)had an improving effect on cognitive impairment caused by sleep deprivation.The changes in neurotransmitter and protein levels in the hippocampus were measured by liquid-mass spectrometry and immunoblotting experiments.It was found that sleep deprivation could induce an increase in GABA levels in the hippocampus of animals,interfere with the PI3K-AKT signaling pathway,affect synaptic plasticity,and may induce cell apoptosis.After administration of ginsenosides Rgl and Rb1,the damage of hippocampus tissue caused by sleep deprivation was reversed.In summary,seven experimental behavioral methods with three different principles were used to analyze and evaluate the cognitive impairment of rats and mice induced by simulation of weightlessness systematically and comprehensively.It was confirmed by different types of behavioral methods that ginsenosides Rgl and Rbl could improve cognitive function damage caused by different types of space stress.Then the mechanism research around mitochondria found that its improvement effect related to the regulation of neurotransmitter levels,mitochondrial division/fusion balance,mitochondrial oxidative phosphorylation function,the process of apoptosis caused by mitochondrial damage,synaptic plasticity.And the characteristics and mechanisms of ginsenoside Rgl and Rbl were compared.Besides,for the first time,a rewarding operation conditioning experiment,which suits the characteristics of astronauts completing complex operations during space flight,was used to found that the complex operation ability was reduced under aerospace stress,and the drug protection function of ginsenosides has been explored.This research provides a new evaluation method for cognitive impairment and protection in a special aerospace environment.It offers an experimental basis for the use of ginsenosides Rgl and Rb1 to improve cognitive function decline in a special aerospace environment and provides a foundation for future long-term in-orbit flight brain recognition.Also,it will give effective protective products for the increase of brain cognition and cognitive ability in the future long-term flying in orbit and methodological support for the research on stress cognitive function impairment in traditional Chinese medicine. |
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